Linking chronic kidney disease and Parkinson's disease: a literature review.

Chronic kidney disease (CKD) has been typically implicated in cardiovascular risk, considering the function the kidney has related to blood pressure, vitamin D, red blood cell metabolism, and electrolyte and acid-base regulation. However, neurological consequences are also attributed to this disease. Among these, recent large epidemiological studies have demonstrated an increased risk for Parkinson's disease (PD) in patients with CKD. Multiple studies have evaluated individually the association of blood pressure, vitamin D, and red blood cell dysmetabolism with PD, however, no study has reviewed the potential mechanisms related to these components in context of CKD and PD. In this review, we explored the association of CKD and PD and linked the components of the former to propose potential pathways explaining a future increased risk for PD, where renin-angiotensin system, oxidative stress, and inflammation have a main role. Potential preventive and therapeutic interventions based on these associations are also explored. More preclinical studies are needed to confirm the potential link of CKD conditions and future PD risk, whereas more interventional studies targeting this association are warranted to confirm their potential benefit in PD.

Does glitazone treatment have a role on the prevention of Parkinson's disease in adult diabetic population? A systematic review.

Lately, focus on the relation between Parkinson's disease (PD) and Diabetes has risen greatly, as neuroprotective properties have been attributed to insulin use. Several studies have assessed the effect of glitazones, an insulin-sensitizing agent, in diabetic population on PD future risk. However, reports on the effect of their use have been heterogeneous. We aimed to synthesize the available scientific evidence which assesses the effect of glitazone use in type 2 diabetes patients on PD incidence. A systematic review was performed on multiple electronic databases. Considered for inclusion were studies that assessed the incidence of PD in type 2 diabetes glitazone users. Two reviewers worked independently and in duplicate to assess all studies, extract information and assess the methodological quality in each included study. Four high quality retrospective cohorts fulfilled inclusion criteria. Comparison groups varied across studies. In each study, incidence of PD was lower in glitazone-exposed patients compared to their respective comparison group. Pooled analysis showed lesser risk of PD in ever versus never glitazone users (RR 0.75 [95% C.I. 0.67-0.85; p < .0001; I2 = 0]). Our pooled analysis showed lesser risk of PD in glitazone versus non glitazone users, however, we advise to take results with caution since results are non-adjusted to possible confounding variables, furthermore, different glitazone-exposure time, follow up and comparison groups are aspects that also need to be pointed out. More clinical research focused on glitazone use and its relation with PD is needed, as this could result in new potential treatment modalities.

"The books and the night", neurological perspective on Jorge Luis Borges' blindness.

The works of Argentinian scholar Jorge Luis Borges (1899-1986) have captivated physicians. An assiduous reader, he was given, with magnificent irony, "books and the night". Borges suffered from chronic and irreversible blindness, which influenced much of his work and has been the subject of different literary and diagnostic analyses from the ophthalmological point of view. However, the characteristics of his visual impairment have escaped the neurological approach, which is why we reviewed his work looking for data suggesting a concomitant brain injury. On his autobiography, he recounts how, during an episode of septicemia, he suffered hallucinations and loss of speech; in addition, in some poems and essays he describes data that suggest "phantom chromatopsia", a lesion of cortical origin. After that accident, Borges survived with a radical change in literary style. Although a precise diagnosis is impossible, his literary work allows recognizing some elements in favor of concomitant brain involvement.

"Los libros y la noche", perspectiva neurológica de la ceguera de Jorge Luis Borges.

The works of Argentinian scholar Jorge Luis Borges (1899-1986) have captivated physicians. An assiduous reader, he was given, with magnificent irony, "books and the night". Borges suffered from chronic and irreversible blindness, which influenced much of his work and has been the subject of different literary and diagnostic analyses from the ophthalmological point of view. However, the characteristics of his visual impairment have escaped the neurological approach, which is why we reviewed his work looking for data suggesting a concomitant brain injury. On his autobiography, he recounts how, during an episode of septicemia, he suffered hallucinations and loss of speech; in addition, in some poems and essays he describes data that suggest "phantom chromatopsia", a lesion of cortical origin. After that accident, Borges survived with a radical change in literary style. Although a precise diagnosis is impossible, his literary work allows recognizing some elements in favor of concomitant brain involvement.

La obra del erudito argentino Jorge Luis Borges (1899-1986) ha cautivado a los médicos. Asiduo lector con magnífica ironía, le fueron dados "los libros y la noche". Borges padeció una ceguera crónica e irreversible que impulsó gran parte de su obra y ha sido objeto de distintos análisis literarios y diagnósticos desde el punto de vista oftalmológico. Sin embargo, las características de su ceguera han escapado al abordaje neurológico, por lo cual revisamos su obra en busca de datos que sugieran una lesión cerebral concomitante. En su autobiografía relata cómo durante un episodio de septicemia padeció alucinaciones y pérdida del habla; además, en algunos poemas y ensayos describe datos que sugieren "cromatopsia fantasma", lesión de origen cortical. Tras dicho accidente, Borges sobrevivió con un cambio radical en su estilo literario. Aunque un diagnóstico preciso es imposible, su obra literaria nos permite reconocer algunos elementos que sugieren involucramiento cerebral concomitante.

Alterations in balance and mobility in people with epilepsy.

PURPOSE: People with epilepsy (PWE) are burdened by physical disability and side effects of antiepileptic drugs (AED) such as drowsiness and blurred vision. These factors place them at risk for reduced mobility and falls. The purpose of this study was to evaluate mobility and balance in PWE. METHODS: This was a cross-sectional study of PWE and age- and sex-matched controls. We evaluated mobility and balance using the Timed Up and Go Test (TUG) and the Tinetti Mobility Test (TMT). Self-reported confidence in balance was assessed using the Activities-Specific Balance Confidence Scale (ABC). Clinical and demographic characteristics and particularly epilepsy-related variables were recorded. RESULTS: We included 33 PWE and 33 controls. PWE had a mean age of 36.7years, and 61% were male. They had a mean of 1.52 of seizures per month and used a mean of 1.6 anti-epileptic drugs (AEDs). PWE scored significantly worse in all measures (TUG, TMT, ABC) when compared with controls. PWE had poor performance in 60.6% of cases in the TUG and in 48.5% of cases in the TMT, compared to none in the control group. There was good correlation between the three instruments. TUG scores were correlated with epilepsy duration, but not age, seizure control or AED use. On multivariate logistic regression, poor performance TMT was significantly associated with poor confidence in balance, according to the ABC. CONCLUSIONS: PWE have significant alterations in balance and mobility, independently of AED use or seizure control. These alterations are reflected in a poor self-reported confidence in carrying out daily activities.

[Time from motor symptoms onset to diagnosis of Parkinson's disease in Mexico]. / Tiempo desde el inicio de los síntomas motores hasta el diagnóstico de enfermedad de Parkinson (EP) en México.

INTRODUCTION: Parkinson's disease is characterized by a wide spectrum of motor and non-motor symptoms with an insidious onset. Identification of these symptoms by the patient as well as by the physician is determinant in order to achieve an early diagnosis. OBJECTIVE: To determine the time from motor symptoms onset to the diagnosis of Parkinson's disease and analyze the clinical and demographic factors related to it. MATERIAL AND METHODS: A cross-sectional study was carried out including subjects with Parkinson's disease seen during the 2011-2012 period and belonging to the Mexican National Parkinson's Registry. Time from symptom onset to the diagnosis was collected; its relation with demographic and clinical characteristics was assessed. RESULTS: A total of 1,062 subjects were included. Delay in diagnosis was 29.5 months. Predictive factors for a longer diagnostic delay were symptoms onset before 40 years of age (B: -0.350; p < 0.001) and a positive family history of Parkinson's disease (B: 0.224; p < 0.001). CONCLUSIONS: The diagnosis of Parkinson´s disease in Mexico is two and a half times greater than what has been reported for other countries.

Building national patient registries in Mexico: insights from the MexOMICS Consortium.

Objective: To introduce MexOMICS, a Mexican Consortium focused on establishing electronic databases to collect, cross-reference, and share health-related and omics data on the Mexican population. Methods: Since 2019, the MexOMICS Consortium has established three electronic-based registries: the Mexican Twin Registry (TwinsMX), Mexican Lupus Registry (LupusRGMX), and the Mexican Parkinson's Research Network (MEX-PD), designed and implemented using the Research Electronic Data Capture web-based application. Participants were enrolled through voluntary participation and on-site engagement with medical specialists. We also acquired DNA samples and Magnetic Resonance Imaging scans in subsets of participants. Results: The registries have successfully enrolled a large number of participants from a variety of regions within Mexico: TwinsMX (n = 2,915), LupusRGMX (n = 1,761) and MEX-PD (n = 750). In addition to sociodemographic, psychosocial, and clinical data, MexOMICS has collected DNA samples to study the genetic biomarkers across the three registries. Cognitive function has been assessed with the Montreal Cognitive Assessment in a subset of 376 MEX-PD participants. Furthermore, a subset of 267 twins have participated in cognitive evaluations with the Creyos platform and in MRI sessions acquiring structural, functional, and spectroscopy brain imaging; comparable evaluations are planned for LupusRGMX and MEX-PD. Conclusions: The MexOMICS registries offer a valuable repository of information concerning the potential interplay of genetic and environmental factors in health conditions among the Mexican population.

[Profile characterization of Parkinson's disease in Mexico: ReMePARK study]. / Caracterización de la enfermedad de Parkinson en México: estudio ReMePARK.

INTRODUCTION: The Mexican Registry of Parkinson´s disease (ReMePARK) is nested within a multicentric cohort aimed to describe motor, non-motor, and genetic determinants of Parkinson's disease in Mexican patients. MATERIAL AND METHODS: To date, clinical and demographic data from 1,083 subjects has been obtained. Here we present the demographic and clinical data of the current sample along with its comparison with international reports. RESULTS: A total of 607 male and 476 female subjects with Parkinson's disease were included. The mean age of the patients was 64.7 ± 12.9 years. The time from onset of symptoms to diagnosis was 2.4 ± 2.6 years. About 34% of subjects had only elementary education. Of the subjects, 54.4% were under treatment with dopamine agonists. CONCLUSION: Subjects with Parkinson's disease incorporated into ReMePARK are comparable with other international registries, with the exception of the years of formal education, time to diagnosis, and the use of dopamine agonists. The characterization of the Mexican population with Parkinson's disease will improve diagnosis and therapeutic management as well as define research efforts in this area. Finally, registry future directions are presented.

MEX-PD: A National Network for the Epidemiological & Genetic Research of Parkinson's Disease.

Background: Parkinson's Disease (PD) has a complex etiology, involving genetic and environmental factors. Most of our current understanding of the disease comes from studies in populations with mostly European ancestry, representing challenges in generalizing findings to other populations with different genetic, social, and environmental contexts. There are scarce studies focused in Latin American populations. The Mexican population is genetically diverse because its admixture from Native American, European, and African ancestries, coupled with the unique environmental conditions, stressing the relevance of establishing genetic studies in this population. Thus, we have established the Mexican Parkinson's Research Network (MEX-PD), a consortium to research the clinical, genetical, environmental, and neurophysiological bases of the phenotypic diversity in Mexican PD patients. Objectives: Describing how MEX-PD was established, the methods and instruments and presenting the first results. Methods: Patients and controls were recruited from medical centers in 20 states of Mexico. Initial recruitment included neurological evaluation, cognitive assessment, and DNA collection. Results: MEX-PD has registered 302 controls and 262 PD patients with a mean age of diagnosis of 61 years (SD=10.86). There were 19.8% PD patients identified with early onset. Levodopa was the most common pharmacological treatment. Conclusions: MEX-PD contributes to understand PD nationally. The information gathered here will allow us to understand the prevalence of mental health, neurological symptoms, and cognitive function in the PD Mexican population and how genetical and environmental factors contributes to those outcomes. These will advocate for personalized treatments and improving quality of life in the Mexican population.

Microalbuminuria as a potential biomarker for Parkinson's disease severity: A hypothesis.

Parkinson's disease (PD) is the second most common neurodegenerative condition characterized by motor and non-motor symptoms causing a great burden in patients' quality of life. PD has been associated with various metabolic factors such as diabetes, hypertension, and more recently chronic kidney disease where proteinuria has been associated with an increased risk. The presence of small amounts of albumin in urine, microalbuminuria, is a common biomarker for endothelial damage and a predictive factor for not only cardiovascular but also neurological dysfunction. Multiple studies have assessed potential biomarkers for PD progression with great heterogeneity, we hypothesize the use of microalbuminuria as a potential marker that correlates with PD severity and might represent a feasible and simple method of evaluating PD patients in clinical practice. Evidence supporting the present hypothesis comes from oxidative stress, insulin resistance, and endothelial dysfunction. Oxidative stress is a key element in PD pathogenesis; studies have shown lower antioxidant capacity as PD progresses. On the other side, insulin signaling plays an important role in neuronal growth and survival, with its resistance being associated with PD. Microalbuminuria has been associated with both processes; increased levels of oxidative stress markers and decreased insulin sensitivity, hence its screening in PD might reflect these common pathological mechanisms. Moreover, the low vitamin D levels observed in PD patients, which are correlated with endothelial dysfunction and disease severity, might contribute to microalbuminuria induction. More evidence on this vascular approach comes from white matter lesions (WML), observed in brain imaging, which have been significantly associated with motor and non-motor function in PD patients and are independently associated with microalbuminuria. In this manner, an oxidant and insulin resistant environment, along with low vitamin D levels in PD patients, which are associated with microalbuminuria, might contribute altogether to WML. As the latter are correlated with motor and non-motor function, microalbuminuria might thus give insight on PD status. Prospective cohort studies with an adequate sample size, follow-up, and a thorough battery of clinical tests for PD are needed to confirm this hypothesis.

Determinants of self-efficacy in patients with Parkinson's disease.

BACKGROUND: Self-efficacy is the individual's assessment of his or hers ability to complete a specific task successfully and has been closely related to self-management and quality of life in several diseases. OBJECTIVE: To investigate self-efficacy in a population of Parkinson's disease (PD) patients in Mexico and study the factors that are associated with this measure. METHODS: We carried out a cross-sectional observational study involving patients with PD in an outpatient neurology clinic in Mexico, using the following instruments: Spanish version of the Chronic Disease Self-Efficacy Scale (CDSES), Quality of Life Questionnaire PDQ-8, Movement Disorders Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), and Non-Motor Symptom Scale (NMSS). Clinical and demographic variables were also recorded. RESULTS: We included 73 patients with a mean age of 65 years and most patients were male. Patients with lower CDSES scores (<7.75) had worse scores in MDS-UPDRS, NMSS, and PDQ-8 scales. CDSES scores were significantly correlated with MDS-UPDRS Part I (r=-0.497, p=<0.001), Part II (r= -0.271, p=0.020), Part III (r=-0.304, p=<0.001), PDQ-8 (r=-0.472, p=<0.001), and NMSS (r=-0.504, p=<0.001). Furthermore, when assessing the simultaneous effect of covariates associated with CDSES score, only Mood/Apathy domain of NMSS was significant (beta= -0.446, t= -3.807, p= 0.012). CONCLUSIONS: PD patients with lower self-efficacy scores had worse motor and non-motor symptomatology and quality of life. Mood/Apathy disorders were negatively associated with self-efficacy and contributed significantly to this measure.

Comparison of the effect of whole-body vibration therapy versus conventional therapy on functional balance of patients with Parkinson's disease: adding a mixed group.

OBJECTIVE: Assess the effect of Whole-Body Vibration (WBV) therapy in functional balance status of Parkinson's disease (PD) patients and compare this to conventional and combined therapy. INTRODUCTION: PD patients experience a decreased mobility, inactivity, and loss of independence as consequence of disturbances in gait, posture, and balance. Rehabilitation therapy is a non-pharmacological way of improving functionality. One of the most studied modalities is WBV, with multiple studies showing improvement in motor function. However, results in this manner are inconsistent. METHODS: Forty-five patients were enrolled in a non-randomized controlled trial and divided into three groups. Group 1 received conventional therapy (thermotherapy, stretching, strengthening, coordination and balance). Group 2 received WBV therapy, and group 3 patients underwent a combined therapy protocol. A total of 20 sessions (3 per week) were conducted, assessing Berg Balance Scale (BBS) before initial and after final session. RESULTS: The 3 intervention groups showed significant improvement in BBS scores after concluding the 20-session trial compared to initial assessment. When comparing mean change in BBS score from initial to final assessment, the combined therapy group had a greater increase compared to conventional therapy, but no significant differences were observed comparing to WBV group. Mean change in BBS score showed no significant difference between conventional therapy and WBV therapy group. CONCLUSIONS: WBV therapy is a useful tool as co-adjuvant in conventional therapy. The combination of both therapies is a significant therapeutic alternative for the improvement of functional balance status in PD patients compared to conventional therapy alone.

Adherence to treatment in Parkinson's disease: A multicenter exploratory study with patients from six Latin American countries.

BACKGROUND: Adherence to treatment in Parkinson's disease (PD) is compromised due to the need for multiple therapies, comorbidities related to aging, and the complexity of therapeutic schemes. In the present study, we aimed to explore adherence to treatment in groups of PD patients from six Latin-American (LA) countries and identify its associated demographic and clinical parameters. METHODS: A multicenter, cross-sectional, exploratory study was conducted from September 2016 to March 2017. Treatment adherence was assessed using the simplified medication adherence questionnaire (SMAQ), applied to patients and caregivers. Sociodemographic and clinical variables (MDS-UPDRS Part III-IV, MMSE, Beck Depression Inventory-II (BDI-II)) were recorded. RESULTS: Eight hundred patients from six LA countries were evaluated. Nonadherence was reported in 58.25% of the population, according to patients. The most frequent issues were forgetfulness and correct timing of doses. A high level of agreement in adherence prevalence and most SMAQ items were observed between patients and their caregivers. The nonadherent population had a significantly higher proportion of unemployment, free access to medication, troublesome dyskinesias and off-periods, lesser years of education, and worse motor, cognitive, and mood scores. In multiple logistic and linear regression analyses, MDS-UPDRS Part III, BDI-II, gender, free access to medication, treatment with dopamine agonists alone, years of education, excessive concerns about adverse effects, and beliefs about being well-treated remained significant contributors to adherence measures. CONCLUSION: Educational strategies, greater involvement of PD patients in decision-making, and consideration of their beliefs and values might be of great need to improve medication adherence in this PD population.

The poor insane Ophelia: reconsidering Ophelia syndrome.

INTRODUCTION: The association between memory loss and Hodgkin's lymphoma has been given the eponym of Ophelia syndrome, in memory of Shakespeare's character in The Tragedy of Hamlet, Prince of Denmark. Nevertheless, there are differences between the disease and the character. OBJECTIVE: To review the origins and uses of the eponym through an original article by pathologist Ian Carr, its relation to the character Ophelia, and the related autoantibodies. METHODS: Historical narrative review. RESULTS: Besides an eloquent description in the original article, Carr presaged the presence of autoantibodies, before they had been thoroughly researched. Since then, five different autoantibodies (mGluR5, Hu, NMDAR, SOX, PCA2) have been associated with Hodgkin's disease. It is interesting to note the divergent outcomes of Shakespeare's character and the patient in the original description by Carr, the latter recovering to lead a normal life, and the former deceased. CONCLUSIONS: Although there is little relationship between the fictional character and the syndrome, both imply the unintentional trigger of self-harm (suicide in one case, autoimmunity in the other), thus remaining associated.

The Parkinson's Disease Sleep Scale-2 (PDSS-2): Validation of the Spanish Version and Its Relationship With a Roommate-Based Version.

BACKGROUND: Because of the prevalence and impact of sleep disorders in Parkinson's disease (PD), valid instruments for their evaluation and monitoring are necessary. However, some nocturnal sleep disorders may go unnoticed by patients themselves. OBJECTIVES: To validate a pan-Spanish version of the Parkinson's Disease Sleep Scale Version 2 (PDSS-2) and to test the relationships between the PDSS-2 and a PDSS-2 roommate version. METHODS: PD patients (n = 399) from seven Spanish-speaking countries were included. In addition to the tested PDSS-2 scales, valid measures for sleep disorders and both motor and nonmotor manifestations were applied. Acceptability, dimensionality, reliability, precision, and construct validity were explored, as well as discrepancies and agreement between the PDSS-2 and the roommate version. RESULTS: PDSS-2 showed negligible floor and ceiling effects. Four factors (57% of the variance) were identified. Reliability parameters were satisfactory: alpha = 0.84; item homogeneity coefficient = 0.27; corrected item total correlation = 0.28 to 0.61; and test-retest reliability (average kappa = 0.70; intraclass correlation coefficient [ICC] = 0.83). The standard error of measurement was 5.84, and correlations with other scales assessing nocturnal sleep were high (rS = 0.62-0.56). In comparison to the patient-based total score, the by proxy total score showed no significant difference, high correlation (rS = 0.70), and acceptable agreement (ICC = 0.69), but there were discrepancies in two or more points in 18% of item scores. CONCLUSIONS: The Spanish version of the PDSS-2 has shown satisfactory clinimetric attributes. Acceptability and precision data are presented for the first time. The PDSS-2 roommate version could be useful to complement the patient-based evaluation, but additional studies are needed.